The invention relates to cyclical peptides that are suited for producing pharmaceuticals for treating cancer. The invention also relates to a method for producing theses compounds and their use as pharmaceuticals.
Until now many cancers cannot be treated by selectively acting biological agents. According to the World Health Organization (WHO) about 10 million people were diagnosed as having cancer in 2000, about 6 million died (World Cancer Report 2003. http://www.iarc.fr/en/publications/pdfs-online/wcr/2003/WorldCancerReport.pdf). According to WHO estimates the number of deaths caused by cancer will rise to about 11.5 million a year by 2030 (Worlds Health Statistics—2007. http://www.who.int/whosis/whostat2007—10highlights.pdf). Starting approximately from 2010, cancer will be the main cause for deaths after infectious diseases, followed by ischemic cardiac diseases, apoplexy (stroke), and HIV/AIDS.
Peptides produced by microorganisms are among promising candidates for treating cancer. For example actinomycin D that is produced by Streptomyces parvulus is already being used a pharamaceutical for treating cancer (BC Cancer Agency Cancer Drug Manual-1994. http://www.bccancer.bc.ca/NR/rdonlyres/852A1FC3-5BD2-481B-BFAA-45ACBFA77FAC/22684/Dactinomycinmonograph—5APR07.pdf). Thiocoralin, a product of Micromonspora marina, inhibits the growth of tumor cells (Romero, F. et al. “Thiocoraline, a New Depsipeptide with Antitumor Activity Produced by a Marine Micromonospora. I. Taxonomy, Fermentation, Isolation, and Biological Activities.” J. Antibiot. 1997; 50 (9): 734-7). The marine fungus isolate Exserohilum rostratum produces the cyclical dipeptides rostratin A-D that are having a cytotoxic effect (Tan, R. X. “Isolation and Structure Assignments of Rostratins A-D, Cytotoxic Disulfides Produced by the Marine-Derived Fungus Exserohilum rostratum.” J. Nat. Prod. 2004 August; 67(8): 1374-82).
Despite the wide knowledge on the species Scopulariopsis even in the marine habitat there is only limited knowledge on natural products from these organisms. As far as we know the only natural product known to date from this species is a pyranol derivate, patented for its antimycotic activity (U.S. Pat. No. 5,270,334).
With a view to the large number of humans that are suffering from cancer, the unfavorable prognosis for curing certain types of cancer (e.g. pancreas) due to the low efficiency of previous pharmaceuticals, side effects, and the development of resistance against pharmaceuticals used there is an urgent need for new cancer pharmaceuticals.